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Chondrosarcoma:Anoverview

AliNajefiST6BTUTeaching19/04/2018

Introduction•  Defini-ons•  Epidemiology•  Types•  Radiology•  Histology•  Treatment•  Prognosis•  Futuredirec-ons

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WhatisaChondrosarcoma?• Chondrosarcomaisamalignanttumorofbonethatischaracterizedbytheproduc7onofcar7lagematrixbytumorcells• Diversehistopathologyandclinicalbehavior• CategorisedtogetherintheWHOclassifica7onasatypicalcar7laginoustumour/chondrosarcomagradeI.

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WHOclassi:ication

Epidemiology •  9%ofallbonetumours•  UKagestandardisedratesreport0.19/100,000popula-on•  2ndmostcommonprimarymalignancyofbone(non-haematological)

•  PrimaryandSecondary•  Primarypeaksaround30-60yearsofage•  Secondarybetween25-45yearsofage

•  Slightlyhigherincidenceinmales•  NoRacePredelic-on•  100-120newcasesperyearintheUK

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Location-Primary•  Pelvis•  ProximalFemur•  ProximalHumerus

•  Canoccurinribsandscapula

•  Althoughrareinhand,mostcommonprimarymalignancyofbonehere.

Location–Secondary(Peripheral)

Secondarylesionsoccuratsitesofbenigncar-lagelesions•  Mul-pleenchondromas•  Ollierdisease–25%byage40•  Maffucci-higher

•  Mul-pleHereditaryExostoses•  Around5%life-merisk•  1%riskforsolitaryenchondromas(Referralbias–trueincidenceunknown)

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SecondaryChondrosarcomaAssociatedwith•  Enchondromas•  Osteochondromas•  Synovialchondromatosis•  Chondromyxoidfibroma•  Periostealchondroma•  Chondroblastoma•  Previousradia-ontreatment•  Fibrousdysplasia

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TypesofPrimaryChondrosarcoma

• Conven-onal(90%)•  Centralorperipheral

• ClearCell• Mesenchymal• Dedifferen-ated

ClearCellCS•  Slowgrowing•  Epiphyseal(especiallyproximalfemur)•  Locallyrecurrenttumour•  Itiso^enconfusedwithchondroblastomaorGCT.•  Metastasesoccuronlya^ermul-plelocalrecurrences.•  Primarytreatmentiswideexcision.•  Systemictherapyisnotrequired.

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MesenchymalCS•  Highgrade•  Predilec-onforflatbones;longtubularbonesarerarelyaffected.

•  Ittendstooccurinyoungerindividualsandhashighratesofmetasta-cpoten-al.

•  The10-yearsurvivalrateis28%.•  Thisen-tyrespondsfavorablytoradiotherapy.•  Treatmentissurgicalremovalcombinedwithadjuvantchemotherapy.

•  Radiotherapyisrecommendedifthetumorcannotbecompletelyremoved.

DedifferentiatedCS•  Approximately10%ofchondrosarcomasmaybededifferen-atedintoafibrosarcomaorosteosarcoma.

•  Thisoccursinolderindividualsandishighlyfatal.•  Surgicaltreatmentiswideexcision•  Adjuvanttherapyiswarranted.

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ClinicalFeatures•  IncreasingPain•  Palpablemass•  Slowgrowing–symptomsmaybepresentformanyyears•  Painwithoutpathologicalfracture–differen-atesenchondromaandchondrosarcoma

RadiographicAppearance

• Margin/paeernofbonedestruc-on • Presence/typeofmatrixmineraliza-on• Cor-calresponse•  So^--ssuemass• Presence/typeofperiostealreac-on

•  Thesiteofthelesionandageofthepa-entmustbeconsidered

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Radiographicappearance•  Arisesinthemedullarycavity•  Irregularmatrixcalcifica-on.•  Thepaeernofcalcifica-onhasbeendescribedas“punctate,”“popcorn,”or“commashaped.”

•  Moreaggressiveappearancethanenchondroma•  Bonedestruc-on,•  Cor-calerosions,•  Periostealreac-on•  So^--ssuemass.

Radiographicappearance•  CTcanbehelpfultoshowendostealerosions]•  MRIshowsso^-ssuecomponent•  Sizeofthecar-laginouscapofanosteochondromawithCTorMRI•  >2cminaskeletallymaturepa-ent

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Enchondroma

Juxtacorticalchondroma

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Osteochondroma

Chondromyxoid:ibroma

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Grade2Chondrosarcoma

Chondrosarcoma

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Chondrosarcoma

Chondrosarcoma

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DedifferentiatedCS

DedifferentiatedCS

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Histology• GradeI,II,orIII.•  Theaggressivenesspredictedbyhistologicgrade.• Gradingsystemisbasedonthreeparameters• Cellularity• Degreeofnuclearatypia• Mito-cac-vity.

EnnekingStaging

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AJCC/UICC

HistologyGrade1

•  Verysimilartoenchondroma.•  Cellularityishigher,andthereismildcellularpleomorphism.

•  Thenucleiaresmallbuto^enshowopenchroma-npaeernandsmallnucleoli.

•  Binucleatedcellsarefrequent.•  Mitosesareveryrare.

Grade1chondrosarcomasarelocallyaggressiveandpronetorecurrences,butusuallydonotmetastasize.

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HistologyGrade2•  ThecellularityishigherthaninGrade1tumors.

•  Characteris-cfindingsaremoderatecellularpleomorphism,plumpnuclei,frequentbi-nucleatedcells,andoccasionalbizarrecells.

•  Mitosesarerare.•  Fociofmyxoidchangemaybeseen.

UnlikeGrade1tumors,about10%to15%ofGrade2chondrosarcomasproducemetastases.

HistologyGrade3

•  Characteris-cfindingsare•  highcellularity•  Markedcellularpleomorphism

•  HighN/Cra-o•  Manybizarrecells

•  Frequentmitoses

ThesearehighgradetumorswithsignificantmetastaNcpotenNal.

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Management

Low-grade•  Extendedcureeagewiththeuseofintraopera-veadjuvanttreatments(phenol,cement,cryotherapy).

•  Low-gradeperipheralchondrosarcomas(arisingfromosteochondromas)shouldbesurgicallyexcised,aimingtoexcisethetumourwithacoveringofnormal-ssueoverit.

•  Thosewithso^--ssueextensionshouldbetreatedsimilartohigh-gradelesions.

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HighGrade•  Wideorradicalresec-onoramputa-on.•  Endoprosthesis•  Thelocalrecurrenceratea^erintraopera-vetumorcontamina-onishigh.

•  Pulmonarymetastasescanbetreatedwithsurgicalresec-onifpossible.

Chemotherapy•  Noroleinthetreatmentofconven-onalchondrosarcoma•  Frequentlyusedfortreatmentofdedifferen-atedandmesenchymalchondrosarcomas.

•  Recentevidencesuggeststhatmesenchymalchondrosarcomamayberesponsivetochemotherapyandmaybeconsideredforadjuvantorneoadjuvanttherapy

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Radiotherapy•  Limitedrole•  Unresectableorinoperable•  Inadequatemargins•  Axialskeletonandpelvicorshouldergirdle,orboth,canbecontrolledbyradia-ontherapy.

•  Chondrosarcomasofthefacialbonesandskullaresuccessfullytreatedwithcombina-onofradiotherapy]

•  MesenchymalChondrosarcoma

Prognosis•  Dependsmostlyonthesize,grade,andloca-onofthelesion.•  Ifincompleteresec-on(usuallybecauseofitssizeorloca-on),localrecurrenceislikely.

•  Low-gradelesionshaveagreaterthan90%10-yearsurvivalrate

•  High-gradeconven-onalchondrosarcomaarereportedtohavea20%to40%10-yearsurvivalrate.

•  The5-yearsurvivalrateislessthan15%forpa-entswithdedifferen-atedchondrosarcoma,withmostdeathsoccurringinthefirst2years.

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Futuredirections

PolychronidouG,KaravasilisV,PollackSM,HuangPH,LeeA,JonesRL.NoveltherapeuBcapproachesinchondrosarcoma.FutureOncol.2017Mar;13(7):637-648.

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Futuredirections•  Theiden-fica-onofIDH1andIDH2muta-onsinchondrosarcomahasledthesetobetargetedwithnew,specificagents,althoughtheeffec-venessandfutureroleofsuchagentsareunclear.•  AmaryMF,BacsiK,MaggianiF,etal:IDH1andIDH2muta7onsarefrequenteventsincentralchondrosarcomaandcentralandperiostealchondromasbutnotinothermesenchymaltumours.JPathol224:334-343,2011

•  Iden-fica-onofMesenchymalchondrosarcomaissupportedbyiden-fica-onofanHEY1-NCOA2fusion,whichcanoccurinbothboneandso^-ssue.Adjuvantchemotherapymayprovideasurvivaladvantage.•  FrezzaAM,CesariM,BaumhoerD,etal:Mesenchymalchondrosarcoma:Prognos7cfactorsandoutcomein113pa7ents.AEuropeanMusculoskeletalOncologySocietystudy.EurJCancer51:374-381,2015

Summary•  Olderagegroup•  Centralorperipheral• Mul-pletypes•  Canbedifficulttodis-nguishfrombenigncar-lagetumours• Matrixcalcifica-on,aggressiveappearance•  Surgeryismainstayoftreatment• MesenchymalchondrosarcomarespondstoCT/RT

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ThankYou

•  UKguidelinesforthemanagementofbonesarcomas,Gerrandetal.ClinSarcomaRes(2016)6:7

•  Campbells13thedi-on,2017•  SarcomasoftheSo^TissueandBone,Mar-nM.Malawer,LeeJ.Helman,and

BrianO’Sullivan,2008•  ImagingofBonetumoursandtumourlikelesions,Baerth,Knaut.Springer.